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. 2022 May 20;42(5):772-779.
doi: 10.12122/j.issn.1673-4254.2022.05.21.

[Interleukin-17A is closely correlated with the progression of renal epithelial-mesenchymal transition in spontaneously hypertensive rats]

[Article in Chinese]
M Xiang  1 , Y Wang  1 , R Mei  1 , J Fu  1 , J Chen  1 , C DU  1
Affiliations

[Interleukin-17A is closely correlated with the progression of renal epithelial-mesenchymal transition in spontaneously hypertensive rats]

[Article in Chinese]
M Xiang et al. Nan Fang Yi Ke Da Xue Xue Bao. .

Abstract
in English, Chinese

Objective: To explore the role of interleukin-17A (IL-17A) in renal epithelial- mesenchymal transition (EMT) in essential hypertensive nephropathy.

Methods: Four-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats (control group) were both randomized into 4 groups (n=5) for observation at 4, 6, 10 and 30 weeks of age. Blood pressure of the rats was monitored using a noninvasive tail artery blood pressure measurement instrument. The percentage of Th17 cells in the splenocytes was analyzed using flow cytometry. The mRNA and protein expression levels of IL-17A, iNOS, Arg-1, E-cadherin, and α-SMA in the kidneys of the rats were detected using RT-PCR and immunohistochemical staining, respectively, and plasma levels of IL-17A were regularly detected using ELISA.

Results: At the age of 6 weeks, the SHRs began to show significantly higher blood pressure with greater Th17 cell percentage in the splenocytes and high renal expression and plasma level of IL-17A than WKY rats (P < 0.05 or P < 0.01). At 30 weeks, renal expression of E-cadherin mRNA and protein was significantly lower and the expression of Arg-1 mRNA and protein was significantly higher in SHR than in WKY rats (P < 0.01). Compared with the WKY rats, the SHRs showed significantly higher mRNA and protein expressions of iNOS at 6 and 10 weeks (P < 0.05 or 0.01) and higher α-SMA mRNA and protein expressions since 10 weeks of age (P < 0.05 or 0.01). In SHRs older than 10 weeks, renal IL-17A mRNA and protein expression levels were negatively correlated with those of E-cadherin (r=-0.731, P < 0.05; r=-0.827, P < 0.01) and positively correlated with those of α-SMA (r=0.658, P < 0.05; r=0.968, P < 0.01).

Conclusion: IL-17A is closely correlated with the progression of renal EMT in SHR and plays its role possibly by mediating M1/M2 polarization of renal infiltrating macrophages.

目的: 探究IL-17A在原发性高血压大鼠肾上皮间质转化（EMT）中的作用。

方法: 4周龄的SPF级自发性高血压大鼠（SHR）（实验组）、京都维斯塔尔大鼠（WKY）（对照组）各20只，分别随机分为4组，每组5只，在4、6、10、30周龄进行实验观察。采用无创尾动脉血压测量仪动态检测大鼠的血压情况；流式细胞技术分析大鼠脾淋巴细胞中Th17细胞的频数；RT-PCR法及免疫组化技术检测大鼠肾脏IL-17A、iNOS、Arg-1、E-cadherin、α-SMA mRNA和蛋白的表达水平；ELISA法检测大鼠血浆中IL-17A的水平。

结果: 从6周龄始SHR大鼠血压显著高于同期的WKY组（P < 0.05或P < 0.01），SHR大鼠Th17细胞频数以及肾脏和血浆中IL-17A的表达亦显著高于同期WKY组（P < 0.05或P < 0.01）；在30周龄时SHR大鼠肾脏中E-cadherin mRNA及蛋白的表达显著低于WKY组（P < 0.01），而Arg-1 mRNA及蛋白的表达显著高于WKY组（P < 0.01）；iNOS mRNA及蛋白的表达在6、10周龄时显著高于WKY组（P < 0.05或P < 0.01），α-SMA mRNA及蛋白从10周龄始显著高于WKY组（P < 0.05或P < 0.01）。SHR大鼠肾脏中IL-17A mRNA及蛋白表达水平从10周龄始与E-cadherin mRNA及蛋白表达水平呈显著负相关（r=-0.731，P < 0.05；r=-0.827，P < 0.01），而与α-SMA mRNA及蛋白表达水平呈显著正相关（r=0.658，P < 0.05；r=0.968，P < 0.01）。

结论: IL-17A与SHR大鼠肾EMT的过程密切相关，可能是通过介导肾脏浸润的巨噬细胞M1/M2极化发挥作用。

Keywords: epithelial-mesenchymal transition; high blood pressure; interleukin-17A; macrophages.

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Figures

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大鼠血压的变化 Changes in blood pressure of the rats with age. *P < 0.05, **P < 0.01 vs WKY group.
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2
大鼠脾淋巴细胞中Th17细胞的频数变化 Frequency of Th17 cells in splenocytes of the rats. A: Flow cytometry. B: Quantitative analysis of the results. *P < 0.05, **P < 0.01 vs WKY group.
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大鼠肾脏中IL-17A、iNOS、Arg-1、E-cadherin、α-SMA mRNA的表达变化 Expression of IL-17A, iNOS, Arg-1, E-cadherin, and α-SMA mRNA in the kidneys of the rats. A: RT-PCR. W: WKY. S: SHR. B: Quantitative analysis of the results. *P < 0.05, **P < 0.01 vs WKY group.
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大鼠肾脏中IL-17A、iNOS、Arg-1、E-cadherin、α-SMA的表达水平 Expression of IL-17A, iNOS, Arg-1, E-cadherin and α-SMA proteins in the kidneys of the rats. A: Immunohistochemical staining of the kidney tissue (Original magnification: ×400). B: Quantitative analysis of the results. *P < 0.05, **P < 0.01 vs WKY group.
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大鼠血浆IL-17A表达水平 Changes of plasma levels of IL-17A in the rats with age. *P < 0.05, **P < 0.01 vs WKY group.
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SHR大鼠肾脏中E-cadherin、α-SMA蛋白及mRNA的表达与IL-17A表达相关性分析（从10周龄始） Correlation analysis of the changes of E-cadherin and α-SMA protein and mRNA expression with IL-17A expression in the kidneys of SHR (after 10 weeks of age). A: IL-17A vs E-cadherin. B: IL-17A vs α-SMA.
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